View source for 7qxo


==The structure of T. forsythia NanH==
<StructureSection load='7qxo' size='340' side='right'caption='[[7qxo]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7qxo]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Tannerella_forsythia Tannerella forsythia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QXO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QXO FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GHD:(2~{R},4~{S},5~{S},6~{S})-5-acetamido-4-oxidanyl-6-[(1~{R},2~{R})-1,2,3-tris(oxidanyl)propyl]-2-[[(2~{R},3~{R},4~{S},5~{R},6~{S})-3,4,5-tris(oxidanyl)-6-[(2~{R},3~{S},4~{R},5~{R})-1,2,4,5-tetrakis(oxidanyl)-6-oxidanylidene-hexan-3-yl]oxy-oxan-2-yl]methoxy]oxane-2-carboxylic+acid'>GHD</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7qxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qxo OCA], [https://pdbe.org/7qxo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qxo RCSB], [https://www.ebi.ac.uk/pdbsum/7qxo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qxo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/G8UIQ1_TANFA G8UIQ1_TANFA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Sialidases are glycosyl hydrolase enzymes targeting the glycosidic bond between terminal sialic acids and underlying sugars. The NanH sialidase of Tannerella forsythia, one of the bacteria associated with severe periodontal disease plays a role in virulence. Here, we show that this broad-specificity enzyme (but higher affinity for alpha2,3 over alpha2,6 linked sialic acids) digests complex glycans but not those containing Neu5,9Ac. Furthermore, we show it to be a highly stable dimeric enzyme and present a thorough structural analysis of the native enzyme in its apo-form and in complex with a sialic acid analogue/ inhibitor (Oseltamivir). We also use non-catalytic (D237A) variant to characterise molecular interactions while in complex with the natural substrates 3- and 6-siallylactose. This dataset also reveals the NanH carbohydrate-binding module (CBM, CAZy CBM 93) has a novel fold made of antiparallel beta-strands. The catalytic domain structure contains novel features that include a non-prolyl cis-peptide and an uncommon arginine sidechain rotamer (R306) proximal to the active site. Via a mutagenesis programme, we identified key active site residues (D237, R212 and Y518) and probed the effects of mutation of residues in proximity to the glycosidic linkage within 2,3 and 2,6-linked substrates. These data revealed that mutagenesis of R306 and residues S235 and V236 adjacent to the acid-base catalyst D237 influence the linkage specificity preference of this bacterial sialidase, opening up possibilities for enzyme engineering for glycotechology applications and providing key structural information that for in silico design of specific inhibitors of this enzyme for the treatment of periodontitis.

Structural and functional characterisation of a stable, broad-specificity multimeric sialidase from the oral pathogen Tannerella forsythia.,Satur MJ, Urbanowicz PA, Spencer DIR, Rafferty J, Stafford GP Biochem J. 2022 Sep 16;479(17):1785-1806. doi: 10.1042/BCJ20220244. PMID:35916484<ref>PMID:35916484</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7qxo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Tannerella forsythia]]
[[Category: Rafferty J]]
[[Category: Satur M]]
[[Category: Stafford G]]